Basketter, D., F. Gerberick, and I. Kimber. Validation in Practice: The Reality for Skin Sensitisation. ATLA 1999. 27: 96.

Chemicals causing skin sensitization, and thus allergic contact dermatitis in man, represent a substantial challenge for toxicologists. Whereas in vivo tests to identify these chemicals have been available for decades, methods for potency evaluation are not well defined. The challenge for the development of in vitro alternatives for skin sensitizing chemicals is complex. Not only is it necessary to identify in vitro systems reflecting the capacity of a chemical to sensitise, but also such methods must provide data on relative sensitizing potency. Computer “expert systems” can identify chemical structural alerts associated with sensitisation hazard, but no in vitro tests possessing that capability exist. Neither approach offers potency information. It is necessary therefore to consider existing assays which provide reduction/refinement benefits for this toxicological endpoint. One such test is the murine local lymph node assay (LLNA), which uses fewer animals than guinea-pig tests and avoids the potentially traumatic aspects of such protocols. The LLNA is as effective for hazard identification as the guinea-pig tests and also offers quantitative data on sensitisation potency. The LLNA validation process provides insights for the acceptance of in vitro alternatives. This validation was actively pursued, yet from test concept to formal acceptance (by ICCVAM in the USA) required 15 years. The validation submission presented data on more than 200 chemicals, with tests conducted at seven laboratories. The submission process required 12 months of intermittent intensive activity at the submitting laboratories and the validation center. It appears that formal acceptance of a skin sensitisation hazard in vitro alternative will require many years before it is validated. Since no such test is even at the stage of prevalidation, clearly it may be many more years before any in vitro test that will provide validated information on skin sensitisation potency is available.